Gray
et al. establish definitively that endocrine disruption occurs
through interaction with androgen receptor, that multiple compounds
are antiandrogens, and that their interaction can produce a diversity
of impacts on the developing male reproductive tract.

These
results are important for several reasons.

They
reinforce the fact that endocrine disruption is not just about
estrogens and estrogenicity.

They
demonstrate that systematic search though compounds in current
use not yet identified as endocrine disruptors yields positive
results... this search is just beginning, and the number revealed
here suggests there will be many more.

They
show that the same compound can have multiple impacts on multiple
components of the reproductive tract.

Among
the results:

One
of the endpoints Grey et al. measured was the percentage
of male pups born with hypospadias (right). Males in the
control group never had hypospadias.

Diethylhexyl
phthalate (DEHP) proved to be highly toxic to the reproductive system
of male offspring in transgenerational studies (in which the pregnant
female was exposed and effects measured in her offspring). "DEHP
induced high levels of testicular and epididymal abnormalities,
including atrophy and agenesis. A striking effect of DEHP was noted
in 8-day old pups. Several males from different litters displayed
hemorrhagic testes that were visible by gross examination of the
inguinal region. Obviously, the testis is a direct target of
DEHP during perinatal life."

Treatment
by procymidone demasculinized and feminized (two separate effects)
the male rat offsprings in a manner nearly identical to that seen
with vinclozolin. The effects included permanent nipples and hypospadias.
Procymidone was more potent than p,p'-DDE, the parent compound of
which (DDT) has been banned since 1976.

The
collection of effects seen in offspring treated by PCB 169 is similar
but more pronounced than exposures caused by TCDD (dioxin). Several
aspects of this work indicate that PCB 169 is not functioning as
an antiandrogen but instead is working through interaction with
the Ah receptor, as does TCDD.

Gray
et al. also determined the percentage of male pups born
with areolas (left). Males in the control group never had
areolas.